Anesth Analg 2005;100:378-381
© 2005 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000144419.44481.59
AMBULATORY ANESTHESIA
The Use of Nicardipine for Electroconvulsive Therapy: A Dose-Ranging Study
Yunan Zhang, MD*,
Paul F. White, MD, PhD, FANZCA*,
Larry Thornton, MD
,
Lisa Perdue, MD, and
Michael Downing, MD*
Departments of *Anesthesiology and Pain Management and Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas
Address correspondence and reprint requests to Paul F. White, MD, PhD, FANZCA, Department of Anesthesiology and Pain Management, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9068. Address e-mail to paul.white{at}utsouthwestern.edu.
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Abstract
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A wide variety of vasoactive drugs have been used to treat the acute hypertensive response to electroconvulsive therapy (ECT). We designed this randomized, double-blind, saline-controlled, crossover study to compare three different doses of nicardipine when administered before the ECT stimulus. Twenty-five patients undergoing a series of 4 ECT treatments received bolus injections of either saline or nicardipine 20, 40, or 80 µg/kg IV in a random sequence during a standardized methohexital (1 mg/kg) and succinylcholine (1 mg/kg) anesthetic technique. The mean arterial blood pressure (MAP) and heart rate values were recorded at specific time intervals, as were the duration of seizure activity and the need for rescue labetalol. Both the 40 and 80 µg/kg doses of nicardipine reduced the percentage increase in MAP above the baseline value compared with the saline group (7% and 7% versus 30%, respectively). Nicardipine 40 and 80 µg/kg were also associated with a significant reduction in the need for labetalol (7 ± 3 mg and 5 ± 0 mg versus 22 ± 10 mg in the saline group). Compared with the 40 µg/kg dose, nicardipine 80 µg/kg was associated with a more rapid heart rate at the time the ECT stimulus was applied. The 80 µg/kg dose was also associated with a reduced MAP value on awakening compared with the baseline value (91 ± 12 mm Hg versus 102 ± 8 mm Hg). We conclude that a bolus injection of nicardipine 40 µg/kg IV immediately before the ECT stimulus was optimal for controlling the acute hemodynamic response to ECT treatments.
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Introduction
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Electroconvulsive therapy (ECT) is routinely associated with significant hypertension and tachycardia (1). A cardiovascular mortality rate of 0.03% has been reported with ECT (2). In patients with preexisting cardiovascular disease, the acute hemodynamic response to ECT may increase the risks of myocardial ischemia and infarction and even cardiac rupture (3,4). Many antihypertensive drugs (including trimethaphan, nitroprusside, nitroglycerin, propranolol, alprenolol, esmolol, clonidine, dexmedetomidine, and nicardipine) have been administered in an attempt to attenuate the acute autonomic response to ECT treatments (5–16). However, the ideal pretreatment regimen to attenuate the acute hemodynamic response after ECT has not been identified.
Nicardipine, a dihydropyridine calcium antagonist, was introduced into clinical practice for use by IV infusion. Therefore, the acute cardiovascular effects of IV bolus doses of nicardipine have not been extensively studied. In a preliminary study involving the administration of nicardipine before the induction of anesthesia for ECT (13), hypotension and tachycardia were observed before application of the ECT stimulus. A subsequent study by Saito et al. (16) suggested that a 20 µg/kg IV bolus dose of nicardipine could control the acute hemodynamic response when administered immediately before application of the ECT stimulus.
We hypothesized that the optimal bolus dose of nicardipine would attenuate the acute hemodynamic effects of ECT without producing either pre- or posttreatment reductions in the patient’s mean arterial blood pressure (MAP). Therefore, the primary objective of this placebo-controlled study was to evaluate the efficacy of three different bolus doses of nicardipine in attenuating the acute hypertensive response to ECT. The secondary objective of the study was to evaluate the effect of nicardipine on the duration of seizure activity.
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Methods
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After IRB approval, 25 consenting patients (ASA physical status I to III) aged 33 to 87 yr who were undergoing a series of 
4 ECT procedures were involved in this study. Patients with clinically significant cardiovascular, respiratory, or hepatic disease; angina; recent (<6 mo) myocardial infarction; or concurrent use of antihypertensive medications and women of child-bearing potential were excluded. According to a crossover randomization scheme, each patient was given saline (control) or nicardipine 20, 40, or 80 µg/kg as an IV bolus injection as part of a standardized anesthetic technique at different ECT treatment sessions.
All patients were premedicated with glycopyrrolate 3 µg/kg IV, and anesthesia was induced with methohexital 1 mg/kg IV, followed by succinylcholine 1 mg/kg IV and labetalol 0.15 mg/kg IV at subsequent 1-min intervals. All patients were ventilated with a face mask and 100% oxygen to maintain an end-expiratory CO2 value between 30 and 32 mm Hg. The study medication (saline or nicardipine 20, 40, or 80 µg/kg IV) was administered 1 min later in a total volume of 2.5 mL (approximately 30–60 s before application of the ECT stimulus). MAP and heart rate (HR) were recorded at 1- to 2-min intervals throughout the periotreatment period. Electroencephalographic (EEG) bispectral index (BIS) values were also recorded at similar intervals. Rescue treatment for increases in MAP >25% of the preanesthesia baseline values consisted of supplemental labetalol (5-mg IV boluses).
A power analysis based on the expected 50% reduction in the need for supplemental labetalol in the largest nicardipine dosage group and the variability observed in a similar study (13) suggested that a group size of 25 should be adequate to demonstrate significant differences from the saline control group. Data were analyzed by using repeated-measures of analysis of variance for continuous variables, with Bonferroni’s correction for multiple comparisons between dosage groups. Data are expressed as mean ± sd. A P value <0.05 was considered statistically significant.
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Results
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The four treatment groups were comparable with respect to age, weight, height, and durations of motor and EEG seizure activity (Table 1). On the basis of their hemodynamic responses during the stimulus titration treatment before entrance into the study, we decided not to give one patient the saline treatment, and two patients did not receive the 80 µg/kg dose of nicardipine because of concerns regarding the possibility of clinically significant hypertensive or hypotensive responses after the ECT stimulus, respectively. Baseline hemodynamic variables were similar in the four treatment groups (Table 2). The EEG BIS values during the periprocedural period did not differ among the four groups (data not reported). These data were similar to previously published data with the same anesthetic technique (17).
In the control group, the MAP and HR were both increased significantly after the ECT stimulus (97 ± 9 mm Hg to 126 ± 23 mm Hg and 81 ± 12 bpm to 124 ± 16 bpm, respectively) (Table 2). In the nicardipine 20 µg/kg group, the MAP increased from 99 ± 10 mm Hg to 120 ± 12 mm Hg, and the HR increased from 78 ± 8 bpm to 120 ± 15 bpm after the ECT stimulus. In the nicardipine 40 µg/kg group, the peak MAP (106 ± 10 mm Hg) and HR (105 ± 20 bpm) after the ECT stimulus were less than in the other three treatment groups (Table 2). In the nicardipine 80 µg/kg group, the peak MAP value was also significantly decreased compared with that in the control group (109 ± 12 mm Hg versus 126 ± 23 mm Hg). However, the MAP value was also significantly decreased on awakening compared with the baseline value (91 ± 12 mm Hg versus 102 ± 8 mm Hg). Finally, there was more need for supplemental labetalol in the control group than in the nicardipine 40 and 80 µg/kg treatment groups (22 ± 10 mg versus 7 ± 3 and 5 ± 0 mg, respectively).
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Discussion
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The current dose-ranging study found that as the nicardipine IV bolus dose was increased from 20 to 80 µg/kg, it produced a dose-dependent decrease in the requirement for labetalol to control the acute hemodynamic response to the ECT stimulus. The smallest dose of nicardipine (20 µg/kg) has been reported to attenuate the acute hemodynamic response after the ECT stimulus (16). However, nicardipine 40 µg/kg IV appeared to be the optimal dose because it was more effective in controlling the acute hypertensive response than the smaller (20 µg/kg) dose and was associated with a lesser increase in HR during the ECT treatments and a lesser decrease in MAP on awakening compared with the 80 µg/kg dose. Presumably, the greater increase in HR in the large-dose nicardipine group was related in part to activation of the baroreflex mechanism as a result of the prominent vasodilatory properties of this calcium channel blocker. The residual hypotensive effects of the larger dose of nicardipine were minimized because this dose was not administered to two patients who had demonstrated enhanced sensitivity to the MAP-decreasing action of nicardipine during the prestudy stimulus-titration treatment.
Many antihypertensive drugs have been administered in an attempt to attenuate the acute circulatory response to ECT (5–16). Although these drugs can reduce the hypertensive response, they are also associated with undesirable side effects, including bradycardia (e.g., esmolol), tachycardia (e.g., nicardipine), hypotension (e.g., nitroglycerin), delayed awakening, and reduced seizure activity (e.g., labetalol and propofol) (1). Although nicardipine has been previously administered alone and in combination with labetalol to attenuate the acute hemodynamic response after ECT (13), this combination produced a significant decrease in MAP immediately before ECT and a lower MAP at the time of discharge from the recovery area. Because of the rapid onset of its hypotensive effect after IV injection, we hypothesized that administering a smaller bolus dose of nicardipine (1.25–2.5 mg IV) immediately before the ECT stimulus would minimize its acute hypotensive action.
As expected, nicardipine did not adversely affect the duration of ECT-induced seizure activity, regardless of the dose administered (13). Because nicardipine is a partially ionized molecule, its failure to decrease the ECT-induced seizure activity or alter the EEG BIS response during the treatment period is probably related to its limited ability to penetrate the blood-brain barrier. Therefore, these data suggest that the routine use of nicardipine should not adversely affect the efficacy of ECT in treating patients with severe depressive disorders.
The persistent increase in HR observed throughout the procedure in all four treatment groups suggests that glycopyrrolate (3 µg/kg IV) was a contributing factor. Given nicardipine’s compensatory effect on HR, it may be unnecessary to administer the anticholinergic drug for routine premedication when this vasoactive drug is administered before the ECT stimulus. Future studies should examine the hemodynamic response to ECT when nicardipine (40 µg/kg IV) is administered with and without glycopyrrolate. Alternatively, a reduced dose of glycopyrrolate (1–2 µg/kg IV) may be effective in reducing oral secretions after the ECT stimulus without producing a persistent increase in HR values. Of interest, a recent case report described the use of a nicardipine 2.5-mg IV bolus to prevent severe bradyarrhythmias associated with hypertension after ECT (18). Finally, nicardipine does not decrease the normal increase in cerebral blood flow velocity after ECT, in contrast to the more commonly used ß-adrenergic blockers (19). This may be an important factor in reducing the risk of cerebral damage due to the seizure-induced increase in cerebral metabolism (20) and hyperemia (16).
In conclusion, nicardipine (40 µg/kg IV bolus) administered immediately before the ECT stimulus in the presence of labetalol (0.15 µg/kg IV) is an effective technique for minimizing the acute hemodynamic response to ECT without adversely affecting the duration of seizure activity or producing undesirable pre- or post-ECT hypotensive effects.
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Footnotes
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Supported by departmental clinical research funds and endowment funds from the Margaret McDermott Distinguished Chair in Anesthesiology.
Accepted for publication August 23, 2004.
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References
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Abstract
Introduction
